T cell response to a variety of immunogens and infectious agents are dominated by cells that produce either IL-4 or IFNgamma. The means through which this preference is established has been studied in in vitro priming of T cells from mice transgenic for T cell receptor alpha and beta chains encoding a receptor for cytochrome c peptide 88-104. The results obtained indicate that IL-4 itself is the major factor that determines the production of IL-4 and that IL-4 suppresses priming for IFNgamma and IL-2 production and promptly suppresses production of these lymphokines. The inhibition appears to be due to a direct action of IL-4 upon activated but not resting T cells. IL-4 also plays a key role in vivo in determining lymphokine-producing phenotype. Treatment of mice with anti-IL-4 antibody at the time of priming with a conventional antigen strikingly suppresses production of IL-4 in response to in vitro challenge with that antigen for from 8 days to 105 days after initial immunization but does not diminish priming for IFNgamma-production. IL-4 is also produced by mast cells and other Fc epsilon RI+ cells. It has been demonstrated that in spleen and bone marrow and in short term cultures of these cells in IL-3, the major IL-4 producing cells expresses Fc epsilon RI but lacks c-kit, indicating that the cell is not a mature mast cell and suggesting that it is a basophil or possibly a mast cell precursor.